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高频的 CD8CD28 T 抑制细胞有助于维持肝移植后移植物功能的稳定和减少免疫抑制剂的剂量。

A high frequency of CD8CD28 T-suppressor cells contributes to maintaining stable graft function and reducing immunosuppressant dosage after liver transplantation.

机构信息

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China.

Division of Liver Transplantation, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China.

出版信息

Int J Med Sci. 2018 Jun 4;15(9):892-899. doi: 10.7150/ijms.24042. eCollection 2018.

DOI:10.7150/ijms.24042
PMID:30008601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6036103/
Abstract

CD8CD28T cells (CD8Ts) exert immunosuppressive effects in various autoimmune diseases. The current study was designed to investigate the role of defects in CD8Ts in liver transplantation (LT). The proportion of CD8Ts in peripheral blood was determined by flow cytometry. The mean proportion of CD8Ts was 23.39% in recipients with stable graft function and 16.64% in those with graft dysfunction following LT compared with 19.86% in the healthy cohort. After receiving enhanced immunosuppressive therapy, patients in the rejection group who achieved recovery of graft function showed an increase in the proportion of CD8Ts (from 17.39% to 25.55%), but those in the group with refractory graft dysfunction showed no significant change (12.49% to 10.30%). Furthermore, in the first year after LT, recipients longer removed in time from the LT date exhibited a higher proportion of CD8Ts. Patients benefited most from tacrolimus concentrations of 5-10 ng/ml in the first year after LT and 0-5 ng/ml thereafter. Moreover, the change in the proportion of CD8Ts (ΔCD8Ts) was significantly higher in recipients with stable graft function than in those with graft dysfunction. These results suggest that a high frequency of CD8Ts prevents rejection and contributes to reduce immunosuppressant dosage and even induces tolerance.

摘要

CD8CD28T 细胞(CD8T 细胞)在各种自身免疫性疾病中发挥免疫抑制作用。本研究旨在探讨 CD8T 细胞缺陷在肝移植(LT)中的作用。通过流式细胞术测定外周血中 CD8T 细胞的比例。与健康队列相比,LT 后移植物功能稳定的受者中 CD8T 细胞的平均比例为 23.39%,而移植物功能障碍的受者为 16.64%。在接受强化免疫抑制治疗后,排斥组中恢复移植物功能的患者 CD8T 细胞比例增加(从 17.39%增加到 25.55%),但难治性移植物功能障碍组无明显变化(从 12.49%增加到 10.30%)。此外,LT 后第 1 年,从 LT 日期及时移除的受者 CD8T 细胞比例更高。患者在 LT 后第 1 年从 5-10ng/ml 的他克莫司浓度中获益最大,此后为 0-5ng/ml。此外,移植物功能稳定的受者中 CD8T 细胞比例的变化(ΔCD8Ts)明显高于移植物功能障碍的受者。这些结果表明,高频率的 CD8T 细胞可预防排斥反应,有助于减少免疫抑制剂的剂量,甚至诱导耐受。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0e/6036103/91385313af9e/ijmsv15p0892g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0e/6036103/0a51fc2a7420/ijmsv15p0892g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0e/6036103/d930544902cb/ijmsv15p0892g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0e/6036103/91385313af9e/ijmsv15p0892g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0e/6036103/0a51fc2a7420/ijmsv15p0892g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0e/6036103/d930544902cb/ijmsv15p0892g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac0e/6036103/91385313af9e/ijmsv15p0892g003.jpg

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本文引用的文献

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Clin Gastroenterol Hepatol. 2017 Apr;15(4):584-593.e2. doi: 10.1016/j.cgh.2016.07.035. Epub 2016 Aug 25.
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Impact of Immune-Modulatory Drugs on Regulatory T Cell.免疫调节药物对调节性T细胞的影响。
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Cancer statistics in China, 2015.《中国癌症统计数据 2015》
心脏移植后 40 年独特的存活期,移植物功能正常且自发产生免疫耐受。
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The Evolving Role of CD8CD28 Immunosenescent T Cells in Cancer Immunology.CD8CD28 免疫衰老 T 细胞在癌症免疫学中的作用不断演变。
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A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation.一项基于调节性 T 细胞的细胞治疗用于活体肝移植中获得免疫耐受的初步研究。
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''Minimizing tacrolimus'' strategy and long-term survival after liver transplantation.肝移植后“最小化他克莫司”策略与长期生存
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